A number of epidemiologic studies have indicated a strong association between
dietary fat intake and
prostate cancer development, suggesting that lipid metabolism plays some important roles in prostate
carcinogenesis and its progression. In this study, through our genome-wide gene expression analysis of clinical
prostate cancer cells, we identified a novel lipogenic gene, ELOVL7, coding a possible long-chain
fatty acid elongase, as overexpressed in
prostate cancer cells. ELOVL7 expression is regulated by the
androgen pathway through SREBP1, as well as other lipogenic
enzymes. Knockdown of ELOVL7 resulted in drastic attenuation of
prostate cancer cell growth, and it is notable that high-fat diet promoted the growth of in vivo
tumors of ELOVL7-expressed
prostate cancer. In vitro
fatty acid elongation assay and
fatty acid composition analysis indicated that ELOVL7 was preferentially involved in
fatty acid elongation of saturated very-long-chain
fatty acids (SVLFA, C20:0 approximately ).
Lipid profiles showed that knockdown of ELOVL7 in
prostate cancer cells affected SVLFAs in the
phospholipids and the neutral
lipids, such as
cholesterol ester. Focusing on
cholesterol ester as a source of de novo
steroid synthesis, we show that ELOVL7 affected de novo
androgen synthesis in
prostate cancer cells. These findings suggest that EVOLV7 could be involved in
prostate cancer growth and survival through the metabolism of SVLFAs and their derivatives, could be a key molecule to elucidate the association between
fat dietary intake and prostate
carcinogenesis, and could also be a promising molecular target for development of new therapeutic or preventive strategies for
prostate cancers.